Multiple Schlerosis Flashcards

Question 1

Q

Define Multiple Sclerosis (MS)

Answer

A

“Multiple” - multiple areas of lost myelin
“Sclerosis” - scarring
MS is a chronic AUTOIMMUNE inflammatory disease affecting the CNS

Question 2

Q

Purpose of myelin sheath and why it’s impactful for MS

Answer

A

Myelin insulate neurons and facilitate nerve conduction efficiency within the CNS.
In MS nerve electrical impulses are affected due to inflammation and immune activity, resulting in demyelination and damage to axons

Question 3

Q

Multiple Sclerosis (MS) Patient Demographics

Answer

A

Usually:
20-50 years old
2.5 : 1 woman to man ratio
Northern European Descent
More common in people living above 40 degrees latitude (vitamin D component possible)
NOT HEREDITARY

Question 4

Q

What nutrient/supplement/vitamin may reduce activity of disease in MS?

Answer

A

Vitamin D

Question 5

Q

Effect of Pregnancy on MS

Answer

A

Seems to have a protective effect

Question 6

Q

Infections that may trigger MS

Answer

A

Epstein-Barr*, HSV-6, canine distemper, measles, Chlamydia pneumonia

*Dr. Rainka had EB underline, remainder probably not critical to know

Question 7

Q

Diagnosing Multiple Sclerosis (MS)

Answer

A

At least 2 documented clinical exacerbations separated by time and space as well as 2 distinct MRI lesions separated by time and space.
• Dissemination in time (DIT) - simultaneous presence of gadolinium enhancing lesions (representing inflammation and disease activity) and non-enhancing lesions or a new lesion on a follow-up MRI when compared to a previous MRI.
• Dissemination in space (DIS) - distinctly different anatomical lesions on imaging occurring in areas known to be affected by MS

Question 8

Q

Clinically Isolated Syndrome (CIS) Diagnosis

Answer

A

CIS is diagnosed after 1 exacerbation and 1 lesion while the clinician awaits a second exacerbation and lesion to be able to make the diagnosis of MS

Question 9

Q

MS Lesion Appearance Terminology on MRI

Answer

A

“Dawson’s Fingers”

Question 10

Q

CSF findings indicative of MS

Answer

A

Intrathecal IgG synthesis and Oligoclonal bands (among other findings)

Question 11

Q

Clinically Isolated Syndrome (CIS) Definition

Answer

A

The first episode of neurologic symptoms lasting at least 24 hours, caused by inflammation and demyelination in one or more sites in the central nervous system. A person with CIS may or may not go on to develop MS

Question 12

Q

CIS

Answer

A

Clinically Isolated Syndrome

Question 13

Q

MS

Answer

A

Multiple Sclerosis

Question 14

Q

RRMS

Answer

A

Relapsing-Remitting Multiple Sclerosis

Question 15

Q

RRMS Definition / Patient Experiences

Answer

A

• Most common, affecting 85% of patients.
• Patients experience worsening of pre-existing symptoms or onset of new symptoms for periods of greater than 48 hours without concomitant fever, known as relapses, flare-ups, or exacerbations, of MS.
• Contrasted by symptom-free periods, known as remissions, where the patient’s symptoms partially or completely disappear.

Refer to colored graph!

Question 16

Q

SPMS

Answer

A

Secondary Progressive Multiple Sclerosis

Question 17

Q

SPMS - Disease Overview

Answer

A

Secondary-Progressive MS

A progression of RRMS
• More common before advent of disease-modifying medications
• Approximately 50% of patients progressed to SPMS after 10-15 years with RRMS
• Incidence has since decreased
This disease course is steadily progressing.
Can present with or without clear-cut relapses.

See Graph!

Question 18

Q

PPMS

Answer

A

Primary Progressive Multiple Sclerosis

Question 19

Q

PPMS - Disease Overview

Answer

A

Primary-Progressive MS
Relatively rare, affecting 10% of patients.
Characterized by steady decline, without clear-cut relapses.
Medications are generally not effective at treating this type of disease.

Question 20

Q

PRMS

Answer

A

Progressive Relapsing Multiple Sclerosis

Question 21

Q

PRMS - Disease Overview

Answer

A

Progressive Relapsing Multiple Sclerosis
Relatively rare, affecting 5% of patients.
Steady disease progression, in addition to clear-cut periods of exacerbations of MS.
Patients can be treated for relapses with steroids, however disease will progress regardless of therapy

Question 22

Q

Treatment for Acute Exacerbation: Acute severe attack

Answer

A

Corticosteroids - NOT disease modifying
A hormone that stimulates the body to make its own hormone and improve its immune system ; Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.
*Methylprednisone (Solumedrol): 1 gram iv infusion per day x 3 to 5 days- may be followed by oral Prednisone taper 60 mg qd x 7 days, then 60 mg qod x 7 days, then 40 mg qod x 7 days, then 20 mg qod x 7 days, then stop
Side effects: jittery/increased energy (something MS patients aren’t used to)
H2 blocker/PPI for ulcer prophylaxis
Monitor blood glucose Watch for infection

Question 23

Q

Treatment for Acute Exacerbation: Acute severe attack (another option)

Answer

A

*Corticotropin Acthar gel: NOT disease modifying
Adrenocorticotropic hormone stimulates the adrenal cortex to secrete adrenal steroids (including cortisol), weakly androgenic substances, and aldosterone
Intramuscular or Subcutaneously: 80 to 120 units/day for 2 to 3 weeks

Question 24

Q

ABCR Injectables - Class of Medications

Answer

A

Interferon Beta
Glatiramer Acetate (pretty sure)
Disease Modifying Agents

Question 25

Q

Interferon beta - Drug Class and MoA

Answer

A

ABCR Injectables

MoA: not fully defined. It may augment suppressor T-cell function; may decrease interferon gamma secretion by activated lymphocytes; may decrease macrophage activating effect; may down-regulate expression of major histocompatibility complex gene production on antigen presenting glial cells.
May also suppress T cell proliferation and decrease blood brain barrier permeability

Question 26

Q

Interferon beta indication

Answer

A

RELAPSING forms of MS including clinically isolated syndrome, RRMS, and “active” SPMS

Question 27

Q

Avonex

Answer

A

Interferon beta-1a
30mcg IM injection dosed weekly
Can titrate to 30mcg to avoid flu-like symptoms

Question 28

Q

Rebif

Answer

A

Interferon beta-1a
SubQ injection TIW
22 or 44 mcg dose

Question 29

Q

Plegridy

Answer

A

Interferon beta-1a
SubQ injection every 14 days
Dose titration up to 125mcg

Plegridy® is pegylated interferon which refers to polyethylene glycol attached to interferon molecules to allow them to maintain their biologic effects in the body for a longer period of time

Question 30

Q

Betaseron

Answer

A

Interferon beta-1b
SubQ injection QOD
250mcg dose after titrating over 6 weeks

Question 31

Q

Extavia

Answer

A

Interferon beta-1b
SubQ injection QOD
250mcg dose after titrating over 6 weeks

Question 32

Q

Interferon beta side effects

Answer

A

FLU LIKE SYMPTOMS - up to 60% of patients. Pre-medicate with Tylenol/ibuprofen to alleviate
Generally worse in females and those with lower body weight
**Depression (not best agent if pt has uncontrolled depression)

Injection site reactions, HA, fever, myalgia, malaise, etc.

Question 33

Q

Glatiramer acetate

Answer

A

Mechanism of Action = Not fully known, thought to be related to alteration of T-cell activation and differentiation. Glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery (potential MoA). May mimic antigenic properties of myelin basic protein; May bind to Major histocompatibility complex class II receptors and inhibit binding of myelin basic protein peptides to T cell receptor complexes; May induce Th2 antiinflammatory lymphocytes and
decrease inflammation, demyelination, and axon damage.
Available as Copaxone,® Glatopa
– Subcutaneous injection given once daily

Question 34

Q

Glatiramer acetate indication

Answer

A

RELAPSING forms including clinically isolated syndrome, RRMS, and active SPMS

Side note: Is NOT an interferon beta agent, is an ABCR injectable

Question 35

Q

Difference between active and inactive SPMS

Answer

A

Some neurologists don’t believe in relapsing nature of SPMS.
Active denotes those with SPMS that relapse

Question 36

Q

Humanized monoclonal antibody

Answer

A

Murine complement sequence only

Question 37

Q

Chimeric monoclonal antibody

Answer

A

Murine antigen binding domain and complement sequence
(See image in notes)

Question 38

Q

Natalizumab MoA & Brand Name

Answer

A

Tysabri

Mechanism of Action = Antagonizes α4-integrin of the adhesion molecule very late
activating antigen (VLA)-4 on leukocytes. Binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4- mediated adhesion of leukocytes to their counter-receptor(s).
**Prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Think of patho of MS (“leaky BBB” that allows body’s natural immune response to target myelin)

Even more effective than interferon beta agents for efficacy

Question 39

Q

Tysabri

Answer

A

Natalizumab
• A humanized monoclonal antibody.
• Intravenous infusion given once every 4 weeks
• Dose = 300 mg

Question 40

Q

Tyruko

Answer

A

Natalizumab=sztn biosimilar to Tysabri

Question 41

Q

Natalizumab indication

Answer

A

RELAPSING forms including clinically isolated syndrome, RRMS, and active SPMS

Question 42

Q

Natalizumab Side Effects

Answer

A

**Progressive Multifocal Leukoencephalopathy (PML) = a sometimes fatal viral opportunistic infection
– Results from activation of the latent John Cunningham polyomavirus in immunocompromised pts
– PML is a demyelinating disease similar to MS, causing impairment of the transmission of nerve impulses, however once myelin is lost in PML, it cannot be regained.

TOUCH Prescribing Program - MRI and symptom monitoring required due to PML risk

Other SEs: infusion rxn, UTI, respiratory tract infection, depression, HA, fatigue, etc.

Question 43

Q

Which agents can cause PML?

Answer

A

Natalizumab
Fingolimod
Dimethyl Fumarate

Question 44

Q

Three risk factors for developing PML

Answer

A

testing positive for antibodies to JCV (John Cunningham Virus, human polyomavirus 2)
prior use of certain immunosuppressant medications
using natalizumab for more than 2 years

Question 45

Q

Alemtuzumab Brand Name

Question 46

Q

Alemtuzumab MoA

Answer

A

Lemtrada
Mechanism of Action = humanized monoclonal antibody. Targets CD52 on T and B lymphocytes, natural killer cells, macrophages and monocytes, causing long-term reduction of circulating T-cells

Question 47

Q

Alemtuzumab Indication

Answer

A

Lemtrada

Indicated for RELAPSING forms of MS, generally reserved for inadequate response to 2 or more (disease modifying) medications

Question 48

Q

Alemtuzumab Administration

Answer

A

Lemtrada
“A reset on the patient’s immune system”

12 mg infused *IV daily over 4 hours for 5 days, then a 3 day course at month 12; patients are observed 2 hours after infusion. Patients can be re-treated again for another 3 days after 12 months

*Premedicate with corticosteroids (methylprednisolone 1,000 mg or equivalent)
* Antihistamines and/or antipyretics may also be considered. Administer antiviral prophylaxis (for herpetic viral infections (16% vs 3% interferon)) beginning on the first day of treatment and continue for at least 2 months after completion of alemtuzumab and until CD4+ lymphocyte count is ≥200/mm3

Question 49

Q

Alemtuzumab Side Effects

Answer

A

Lemtrada

*DEVELOPMENT OF Autoimmune THYROID DISORDERS
 Including GRAVES’ DISEASE requiring thyroid ablation
 In 1/3 of patients
 For MS, monitor TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated.
*Rash in 90% of patients
Others: infections, dizziness, HA, N/V/D, etc.

Question 50

Q

Alemtuzumab BBW

Answer

A

Lemtrada

BBW:
- autoimmune conditions, such as immune thrombocytopenia and anti-glomerular basement membrane disease.
- ischemic/hemorrhagic stroke within 3 days of dose admin
- Infusion reactions (Lemtrada): Alemtuzumab causes serious and life-threatening infusion reactions (92%). must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for 2 hours after each infusion.
- Malignancy

Question 51

Q

Alemtuzumab Monitoring

Answer

A

Lemtrada

CBC with differential prior to initiation then monthly until 48 months after last infusion; serum
creatinine prior to initiation then monthly until 48 months after last infusion or at any time during
therapy if clinically indicated;
Urinalysis with urine cell counts (prior to initiation then monthly); signs/symptoms of infection;
TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated;
Observe for at least 2 hours after each infusion, longer if clinically indicated;
ECG prior to each treatment course
No live vaccines, wait 6 weeks after VZV
Annual HPV screening (2%)
Signs/symptoms of PML
Baseline and annual skin exams (for melanoma).

Question 52

Q

Daclizumab

Answer

A

Taken off the market

Question 53

Q

Anti CD 20 Monoclonal Antibodies

Answer

A

Ocrelizumab
Ublituximab
Ofatunumab

Question 54

Q

Ocrelizumab Brand Name

Question 55

Q

Ocrelizumab MoA, RoA

Answer

A

Ocrevus
Monoclonal Antibody
MOA: binds to (CD20) on the surface B cells, and depletes them from circulation
RoA: IV 600mg every 6 months (after 300mg OD1 and 300mg 2 weeks later)

Similar to rituximab, but
• Increased antibody-dependent, cell-mediated cytotoxic effects.
• Potentially less immunogenic

Question 56

Q

Ocrelizumab Indication

Answer

A

Ocrevus

Significantly reduce relapse rates, disability progression and disease activity on MRI in patients with RRMS and SPMS
Reduce disability progression 24%, time required to walk 25 feet, volume of brain lesions and whole brain volume loss in PPMS in the ORATORIO phase III trial. This is the first large scale trial to show positive results in PPMS

Indication: PPMS and relapsing forms of MS, including CIS, RRMS, and active SPMS
(Didn’t remember the ** parts? Mark this as wrong!)

Question 57

Q

Ocrelizumab Side Effects

Answer

A

Ocrevus

Most common adverse events = INFUSION REACTIONS
Patients were PRE-MEDICATED with *steroids (methylprednisolone 100 mg IV 30 min prior), *antipyretics (APAP), and *antihistamines (diphenhydramine 30-60 min prior)

Question 58

Q

Ocrelizumab Contraindications/Warnings

Answer

A

Ocrevus
CI: active hepatitis B virus (HBV) infection. Screen patients before starting
NO cases of PML found in studies with Ocrelizumab

Question 59

Q

Ublituximab Brand Name

Question 60

Q

Ublituximab MoA + Indication

Answer

A

Biumvi
MoA: chimeric IgG monoclonal antibody directed against the CD20 antigen on pre-B and mature B lymphocytes. Ublituximab binds to CD20 and results in cell lysis via complement-dependent cytolysis and antibody-dependent cellular cytolysis.

Indication: relapsing forms of MS including CIS, RRMS, active SPMS

Question 61

Q

Ublituximab Safety, Contraindication(s) and Administration

Answer

A

Biumvi
Safety: screen all patients for hepatitis B virus, hepatitis B core antibody, and latent infections. Pregnancy testing recommended before each dose.
CI: Active HBV infection (think uBlituximab, no Hep B!)

Administration: PREMEDICATE with methylprednisolone 100mg IV, antihistamine, and may consider antipyretic (acetaminophen) all ~30 minutes prior to dose
Given IV 150mg OD1, 450mg 2 weeks later, then 450mg q24 WEEKS

Question 62

Q

Ublituximab Warnings/Precautions

Answer

A

PML
Polysorbate 80 (ingredient, not a main focus)
Immunizations (live 4 weeks before, non-live 2 weeks before, no live or live attenuated during treatment or after D/C until B-cell repletion)

Question 63

Q

Ofatunumab Brand Name

Question 64

Q

Ofatunumab MoA and Administration

Answer

A

Kesimpta
MoA: Ofatumumab is a monoclonal antibody which binds specifically the extracellular (large and small) loops of the CD20 molecule (which is expressed on normal B lymphocytes and in B-cell CLL) resulting in potent complement-dependent cell lysis and antibody-dependent cell-mediated toxicity in cells that overexpress CD20.

Administer all live or live-attenuated vaccines at least 4 weeks prior and non-live vaccines at least 2 weeks prior to initiation of therapy. Screen for hepatitis B prior to initiation; do not administer to patients with active hepatitis B confirmed by hepatitis B surface antigen (HBsAg) and anti-hepatitis B virus (HBV) tests.

Administer only by SubQ injection in the abdomen, thigh, or outer upper arm one time per MONTH. Patients may self administer

Answer 61

A

Kesimpta
Warnings: Females of reproductive potential should use effective contraception during therapy and for 6 months after the last dose of ofatumumab.
PML risk
Adverse Effects: Infection (52%) and URTI (39%)

Answer 62

A

Mitoxantrone
Cladribine

Answer 63

A

Novantrone

Answer 64

A

Mechanism of Action = Intercalates with DNA strands causing breaks, and inhibits DNA repair through topoisomerase II.
– Affects rapidly dividing cells -> secondary effects on the immune system

**Indication: SPMS, PRMS, or worsening of RRMS to reduce neurologic disability and/or the frequency of clinical relapse
**Limitation of use: not indicated for the treatment of PPMS. Reserve use for rapidly-advancing, refractory multiple sclerosis

Different indication than other agents!

Answer 65

A

Novantrone
Chemically related to doxorubicin and daunorubicin
Positive Evidence of Risk (Pregnancy Category D)
– Intravenous infusion given once every 3 months

Side Effects: Cardiotoxicity , bone marrow suppression, others…

Answer 66

A

Mavenclad
(2-chlorodeoxyadenosine)

Answer 67

A

Treatment of relapsing forms of multiple sclerosis, (RRMS) and active SPMS in adults who have had inadequate response or are intolerant to other therapies for multiple sclerosis. Must have failed something else
Not recommended for patients with clinically isolated syndrome

MoA: Cladribine is a purine nucleoside analogue; it is a prodrug which is activated by phosphorylation and converted into the active moiety, Cd-ATP. This active form incorporates into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis and repair. This also results in a depletion of nicotinamide adenine dinucleotide and adenosine triphosphate (ATP). Cladribine is cell-cycle nonspecific. The mechanism of cladribine in treating multiple sclerosis (MS) is unknown, but may involve cytotoxic effects on B and T lymphocytes that result from the shutdown of DNA synthesis, leading to a depletion of lymphocytes.

Answer 68

A

10 mg ORAL tablets
Usual dosage: 3.5 mg/kg over 2-year treatment course, administered as 1.75 mg/kg in each year.
• Divide the 1.75 mg/kg dose over 2 cycles, each cycle lasting 4 to 5 consecutive days

Lymphocytes must be within normal limits before initiating first treatment course and ≥800 cells/mm3 before initiating the second treatment course.

Patients should use dry hands for handling and avoid prolonged contact with skin; wash hands and any surface that came in contact with the tablet thoroughly afterwards. Separate administration from any other oral medication by 3 hours.
Hazardous agent (NIOSH 2016 [group 1]).

Answer 69

A

*Malignancies (cancer)
*Teratogenicity - CI in pregnant women. women/men of reproductive potential - use effective contraception during cladribine oral tablets dosing and for 6 months after the last dose
HIV infection
Active Chronic Infections (e.g. hepatitis or tuberculosis)

Low MW and Low protein binding = likely crosses into breast milk

Answer 70

A

Malignancy + Pregnancy (boxed warning)
Bone Marrow Suppression
Infection
PML
Vaccines
Graft-versus-Host Disease
Hepatotoxicity
Cardiotoxicity
Drug Interactions
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1

Answer 71

A

CBC including lymphocyte count (before each treatment course, 2 and 6 months after the start of each yearly course)
evaluate HIV, tuberculosis, hepatitis B (HBV) and hepatitis C (HCV) status (prior to each treatment course);
evaluate varicella-zoster virus (VZV) antibody status (prior to treatment initiation);
pregnancy test (prior to treatment in females of reproductive potential);
liver function tests (serum aminotransferase, alkaline phosphatase and total bilirubin levels) (prior to each treatment course and as clinically appropriate)
MRI (at baseline [within 3 months] prior to first treatment course); signs or symptoms of progressive multifocal leukoencephalopathy (PML)
standard cancer screening;
signs or symptoms of acute infection.

Answer 72

A

All ORAL agents
Fingolimod
Siponimod
Ozonimod

Answer 73

A

Gilenya

Tascenso ODT = bioequivalent to Gilenya

Answer 74

A

Gilenya

Mechanism of Action = Acts on the sphingosine-1-phosphate (S1P) receptors S1P1 and S1P3-5 on the surface of lymphocytes
-Depletes both CD4+ and CD8+ T lymphocytes in the blood stream, up to 75% below baseline.
-CD4+ cells are decreased to a greater extent than CD8+ cells.
-Inhibits lymphocyte release from lymphatic organs decreasing overall numbers in circulation
Note: they’re still there, just contained in lymphatic organs

Indication: relapsing forms of multiple sclerosis, including CIS, RRMS, and active SPMS, in patients ≥10 years of age

Answer 75

A

Gilenya
ORAL Therapy for MS, 0.5mg PO QD
First Dose Monitoring: ECG needed before initiating. Monitor hourly for 6 hrs post 1st dose for bradycardia— take HR and BP
* Repeat 1st dose monitoring if patient misses 1 day in first 2 weeks, 7 days in 3rd and 4th weeks, or 14 days after 1 month

Contraindicated: recent MI, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III or Class IV heart failure. history of Mobitz Type II second or third degree AV block or sick sinus syndrome (unless patient has a pacemaker), baseline QTc greater than 500 msec, or with concurrent treatment with Class Ia or Class II anti-arrhythmic drugs

Patients without antibodies who wish to become vaccinated against varicella zoster should wait 30 days after vaccination before receiving fingolimod as patients on fingolimod should not receive live vaccines.

Macular Edema (pt should receive baseline eye exam and checkups), other common AEs

Answer 76

A

Mayzent
Treatment of relapsing forms of multiple sclerosis (MS), including CIS, RRMS, and active SPMS, in adults
MoA: a sphingosine-1-phosphate (S1P) receptor modulator, binds to sphingosine 1-phosphate receptors 1 and 5. Siponimod blocks the lymphocytes’ ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the CNS is decreased, which reduces central inflammation

Answer 77

A

Mayzent
ORAL Dosing - patient MUST undergo genotype testing (2C9 - NINE)

CYP2C9 Genotype 1/1, 1/2, or 2/2
Maintenance dosage: 2 mg QD, beginning on Day 6

CYP2C9 Genotype 1/3 or 2/3
Maintenance dosage: 1 mg QD, beginning on Day 5

CYP2C93/3 genotype contraindicated

First dose monitoring recommended, but NOT required like for fingolimod

Answer 78

A

Contraindications: CYP2C93/3 genotype; recent (in the past 6 months) MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker

Answer 79

A

Mayzent
* Immunizations: Testing antibodies to (VZV) is recommended prior to initiation of treatment if history of chickenpox or VZV vaccination status is unknown* Wait 4 weeks for live vaccination
Infections
PML
Macular Edema - just like fingolimod
Atrioventricular conduction delays
QT Prolongation
CVD, HTN, Bradycardia
Respiratory/Hepatic Effects
Neurotoxicity
Malignancy
DDIs
* Discontinuation of therapy - Cases of rebound syndrome (clinical and radiological signs of severe exacerbation beyond what was expected) have been reported with discontinuation of another sphingosine 1-phosphate receptor modulator

Answer 80

A

Mayzent
Drug-drug interactions Extensively metabolized, mainly via CYP2C9 (79.3%), followed by
CYP3A4 (18.5%) to inactive metabolites, M3 and M17
Immunosuppressants
Bradycardia-causing agents
AV blocking agents
QT prolonging agents
2C9/3A4 inducers may decrease concentration
2C9/3A4 inhibitors may increase concentration

Answer 81

A

Mayzent
No. May cause fetal harm. Disease modifying therapies are generally not initiated during pregnancy . Females of reproductive potential should use effective contraception during therapy and for 10 days after the last siponimod dose.
~2 months for Fingolimod
~3 months for Ozonimod

Answer 82

A

Mayzent
All patients: CBC including lymphocyte counts, hepatic, ecg, ophthalmic exam, respiratory function, VZV antibodies, BP, s/s infection or PML, suspicious skin lesion monitoring

First dose monitoring only in select patients:
Additional required monitoring for patients with sinus bradycardia (HR <55 bpm), first- or second-degree (Mobitz type 1) AV block, or a history of MI or heart failure

Answer 83

A

Cases of progressive multifocal leukoencephalopathy (PML) due to the John Cunningham virus have been reported in patients taking sphingosine 1- phosphate receptor modulators. Risk factors for development of PML include HIV, AIDS, cancer history, rheumatologic disease history, persistent lymphocytopenia, sarcoidosis, and prior immunosuppressant use (Jamilloux 2014; Tan 2010). At the first sign or symptom suggestive of PML, perform a diagnostic evaluation and withhold therapy; symptoms progress over days to weeks and may include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, and mental status changes. Cases of PML have been diagnosed based on MRI findings without specific PML signs/symptoms. Monitoring with brain MRI for signs that may be consistent with PML may be beneficial and allow for an early diagnosis of PML. Discontinue treatment if PML is confirmed.

Answer 84

A

Zeposia
Lots of duplicate info from other S1P drugs, will highlight main differences on other Ozonimod cards
MoA: Ozanimod has a high affinity to sphingosine 1-phosphate receptors 1 and 5. Ozanimod blocks the lymphocytes’ ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the CNS is decreased.
Administration: ORAL Dosing. Maintenance dose: 0.92 mg once daily starting on day 8. Note: If a dose is missed during the 2-week titration period, reinitiate the titration regimen with 0.23 mg once daily. If a dose is missed after the first 2 weeks of treatment continue with treatment as planned.
If live attenuated vaccine immunizations are required prior to administration, initiate ozanimod therapy at least 1 month following immunizations

Contraindications: Myocardial infarction, unstable angina, stroke, transient ischemic attack,
decompensated heart failure (HF) requiring hospitalization, or class III or IV HF in the last 6
months; Mobitz type II second- or third-degree atrioventricular block, sick sinus syndrome, or
sinoatrial block, unless the patient has a functioning pacemaker; severe untreated sleep apnea;
concomitant use of a monoamine oxidase inhibitor

Answer 85

A

Females of childbearing potential should use effective contraception to avoid pregnancy during therapy and for 3 months after discontinuing treatment.
Fingolimod ~2 months
Siponimod 10 days

Answer 86

A

Zeposia
* Concurrent ingestion of foods and beverages with very high amounts of tyramine (ie, >150 mg) may cause sudden and severe high BP (hypertensive crisis). Management: Avoid foods with very high tyramine content.
***Contraindicated in use with MAOi’s (selegiline, rasagiline, isocarboxazid, etc.)

Clinical trials show Versus Avonex, (maybe important to know?)
Decreased ARR
Decreased Gd+ lesions
Decreased new or enlarging T2 lesions

Answer 87

A

Ponvory
Sphingosine 1-phosphate (S1P) receptor 1 modulator, binds with high affinity to S1P receptor 1.

Cardiac monitoring: First-dose 4-hour monitoring is recommended for patients with certain preexisting cardiac conditions, including sinus bradycardia (heart rate <55 bpm), first- or second-degree (Mobitz type 1) atrioventricular block, or a history of myocardial infarction or heart failure ≥6 months prior to initiation
Don’t start in active infection, like with other S1P receptor modulators

Missed dose: ≥ 4 consecutive doses missed: Reinitiate treatment with day 1 of the initial titration regimen, including first-dose monitoring when appropriate.

Answer 88

A

-Basal cell carcinoma and other skin malignancies (including malignant melanoma and squamous cell carcinoma of the skin) have occurred rarely with ponesimod.
-Increased serum transaminases have been observed with ponesimod therapy, primarily as increased serum alanine aminotransferase (ALT), including increases up to 5 x ULN.
-Reversible lymphocytopenia occurs during ponesimod therapy. Infection is commonly observed with use, typically upper respiratory tract infection and less commonly urinary tract infection; viral infections (eg, herpes virus infection) have also been observed
-Reduced forced expiratory volume over 1 second (FEV1) and reductions in diffusion lung capacity for carbon monoxide have occurred with ponesimod therapy

Answer 89

A

Aubagio
Blocks pyrimidine synthesis in rapidly dividing cells, inhibits protein tyrosine-kinase and cyclo-oxygenase-2 activity, and decreases the ability of antigen presenting cells to activate T-cells.

Inhibition of pyrimidine synthesis selectively produces a cytostatic effect on proliferating T and B lymphocytes in the periphery, while avoiding undue cytotoxicity to other cell types. Teriflunomide effectively reduces B-lymphocyte proliferation

Indication: oral therapy for RRMS and SPMS - Doses = 7 and 14 mg
Also says for CIS on Lexicomp

Answer 90

A

Aubagio
Lots of SEs, Highlighted in class:
*Alopecia
*Increases in LFTs
BBW: Hepatotoxicity, teratogenicity – Category X for Pregnancy

Answer 91

A

Aubagio

Accelerate elimination with cholestyramine 8 or 4 g q 8h x 11d or
50 g activated charcoal q12 h x 11 d
– Decrease conc by 98%
– Without reversal agent, the drug lasts in the body for 8 mo-2 years

Answer 92

A

Aubagio

**The dose of rosuvastatin should not exceed 10 mg in patients on teriflunomide.
Teriflunomide may decrease INR in patients taking warfarin.

Answer 93

A

Dimethyl fumarate (Tecfidera)
Diroximel fumerate (Vulmerity)
Monomethyl fumerate (Bafiertam)

Answer 94

A

Tecfidera
MoA: Induces T-helper 2-like cytokines (including interleukins 4, 5, and 10) causing
– Apoptosis in activated T cells and
– Down-regulation of intracellular adhesion molecules, leading to reduced migration of lymphocytes.
DMF and its active metabolite, monomethyl fumarate (MMF), have been shown to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is involved in cellular response to oxidative stress

Answer 95

A

Tecfidera

Approved as an oral therapy for relapsing forms of MS including CIS, RRMS, and active SPMS
Dose = 120mg PO BID for 7 days, then 240mg PO BID
Dimethyl fumarate treatment decreased number of new T1, new T2, and Gd+ lesions on MRI

Answer 96

A

Tecfidera
GI SYMPTOMS!!! Administer with or without food; administering with high-fat, high-protein food (eg, yogurt or peanut butter) may decrease the incidence of flushing and GI effects
Flushing - Administration of aspirin (nonenteric coated up to a dose of 325 mg) 30 minutes prior to dimethyl fumarate may also reduce the incidence of flushing
Transient increases in LFTs

Lymphopenia
– Recent CBC (within 6 months) needed before treatment, then q 3 mo therafter and as
clinically indicated.
– Lymphocyte count <500/mm3 persisting for >6 months: Consider treatment interruption.
– MRI (baseline and as clinically indicated to monitor for early signs of progressive multifocal
leukoencephalopathy [PML]).

Answer 97

A

Vumerity
-Bioequivalence to dimethyl fumarate (Tecfidera)
-Maintenance dose of 462 mg twice daily.
-Unique structure that rapidly converts to monomethyl fumarate in the body. As a result, the drug causes less gastrointestinal (GI) irritation
-May administer aspirin (nonenteric coated ≤325 mg) 30 minutes prior to diroximel fumarate to reduce the incidence or severity of flushing.
-A high-fat (>30 g), high-calorie (>700 calories) meal may significantly DECREASE the maximum concentration of the major active metabolite, monomethyl fumarate (MMF)

Answer 98

A

Bafiertam
-“Bioequivalent alternative” to Biogen’s Tecfidera® (dimethyl fumarate) - site of action and active ingredient don’t differ significantly
-Maintenance dose: 190 mg twice daily
-Non-enteric coated aspirin up to 325mg can be used for flushing
**Unique to this product: Store unopened bottles in refrigerator , opened at room temp

Answer 99

A

Spasticity
OAB/Urinary Retention
Sensory (paresthesias, neuropathic Pain)
Fatigue/cognitive issues/ Emotional issues
Pseudobulbar Affect (PBA)
Walking

Answer 100

A

Antispasmodics
• Baclofen
• Dantrolene
• Diazepam, clonazepam
• Tizanidine
• Gabapentin, tiagabine, pregabalin
• Botox
• Dalfampridine
(Not sure we have to know all these)

Answer 101

A

Recall: MS patients have cognitive impairment, beware which agents you choose!
(Just skim through)

• Propantheline - Propantheline bromide inhibits gastrointestinal motility and diminishes gastric acid secretion. The drug also inhibits the action of acetylcholine at the postganglionic nerve endings of the parasympathetic nervous system
• Oxybutynin - antimuscarinic
• Dicyclomine/Bentyl - Dicyclomine is an antispasmodic and anticholinergic (antimuscarinic) agent
• DDAVP - DESMOPRESSIN ACETATE ( 1-Deamino-8-D-Arginine Vasopressin), Desmopressin is a
synthetic analog of the natural pituitary hormone arginine vasopressin, an antidiuretic hormone
affecting renal water conservation
• Cathetherization
• Imipramine/amitriptyline
• Prazosin -inhibits postsynaptic alpha-adrenergic receptors
• Botox
• Solifenacin/Vesicare - anticholinergic
• Darifenacin/Enablex - anticholinergic
• Trospium / anticholinergic
• Hyoscyamine - anticholinergic
• Fesoterodine/Toviaz– anticholinergic
• Mirabegron (Myrbetiq) is a novel selective human beta-3-adrenergic receptor agonist that relaxes the detrusor smooth muscle and increases bladder storage capacity. It has been shown to be efficacious in a small study of MS patients who has previously experienced low efficacy with antimuscarinics

Answer 102

A

• Carbamazepine, oxcarbazaepine
• Phenytoin
• TCAs
• Gabapentin
• Lamotrigine
• Pregabalin
• Duloxetine

Answer 103

A

• Amantadine
• SSRI/SNRI
• Modafanil
• Methylphenidate
• Dextroamphetamine

Answer 104

A

Characterized by uncontrollable episodes of crying or laughing

Treatable by Nuedexta (Dextrometorphan HBr and Quinidine Sulfate) 20/10mg 1 cap PO BID maintenance dose

Exact MoA unknown, thought to inhibit glutamatergic neurotransmitter via action at variety of locations including NMDA receptor and sigma-1 receptors
- Quinidine helps with blocking metabolism of dextrometorphan (2D6), therefore increasing serum concentrations of dextromethorphan (1-3% of dose used to treat cardiac arrhythmias)

Answer 105

A

Dalfampridine (Ampyra) – (4-aminopyridine)
Dose: 10 mg BID - Tablets should only be taken whole
*Broad-spectrum potassium channel blocker
*Increase conduction of action potentials in demyelinated axons through inhibition of potassium channels
Contraindicated: History of seizure; Moderate to severe renal impairment (was on our first exam!)

Answer 106

A

Schedule 1 Federal Controlled Substance - makes research with it harder

Strong evidence OCE (oral cannabinoid extracts) in spasticity scores
Strong evidence OCE in central pain

Summary, cannabinoids may be effective for spasticity, MS-related pain, painful spasm, and bladder voiding. Cognitive impairment, can deter product use, particularly in patients already experiencing cognitive difficulties.

Answer 107

A

Ocrelizumab (Ocrevus) - CD20 mab

Answer 108

A

Ofatunumab (Kesimpta)

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